This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our prior investigation of adults with chronic localization-related (temporal lobe) epilepsy and healthy controls has shown childhood onset epilepsy to be associated with a generalized adverse neurodevelopmental impact on brain structure and cognitive function (NS-37738). The purpose of this proposal is to directly characterize the timing, cause and consequences of this adverse neurodevelopmental impact. Using a combined cross-sectional and longitudinal design, 75 children (age 8-18) with new onset localization-related epilepsy will be compared to 75 age and gender matched controls. Cross-sectional and two-year longitudinal assessment of neuropsychological status and neuroimaging (quantitative MRI, diffusion tensor imaging, and magnetization transfer imaging) will be integrated with information regarding neurodevelopmental history, clinical epilepsy characteristics and psychiatric morbidity in order to clarify the timing, etiology and consequences of evident abnormalities in brain structure and cognition. We hypothesize the following: (1) children with new onset localization-related epilepsy will exhibit generalized cognitive impairment, generalized reduction in total brain tissue volumes (especially cerebral white matter volumes), and microstructural abnormalities in cerebral white matter compared to controls, (2) frequency of preexisting neurodevelopmental abnormalities will be significantly increased in children with new onset epilepsy compared to controls and will be associated with neuroimaging and cognitive abnormalities at epilepsy onset, (3) ongoing childhood onset epilepsy will be associated with lags in normal cognitive and brain development (especially cerebral white matter) and increased psychiatric morbidity compared to controls, and (4) earlier age of epilepsy onset will be the strongest predictor of lags in brain growth and cognitive development while seizure severity will be most strongly associated with increased psychiatric morbidity.